Research goals for the coming year are as follows: a. To study some of the detailed steps in the enzymatic replication of mitochondrial DNA, using various combinations of three mitochondrial enzymes, namely DNA polymerase (termed by some, gamma-polymerase), nicking-closing enzyme (which is probably a Type I topoisomerase), and our catenating-knotting enzyme (probably a Type II topoisomerase). b. To purify the two topoisomerases to homogeneity and study their properties further, particularly those of the Type II enzyme which we have only recently isolated. c. To accomplish our previously set goal of elucidating the effect of evolutionary mutations in mtDNA, particularly in view of the fact that the three mutations we have studied thus far do not lead to changes in gene products. d. To use the phenomenon of mtDNA polymorphism to study the mechanism of maternal inheritance. We have shown that maternal inheritance operates in mammals; we now ask the question, what happens to the paternal mitochondrial DNA?